Skip to main content
SpringerLink
Log in

Application of microbioreactors in fermentation process development: a review

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Biotechnology process development involves strain testing and improvement steps aimed at increasing yields and productivity. This necessitates the high-throughput screening of many potential strain candidates, a task currently mainly performed in shake flasks or microtiter plates. However, these methods have some drawbacks, such as the low data density (usually only end-point measurements) and the lack of control over cultivation conditions in standard shake flasks. Microbioreactors can offer the flexibility and controllability of bench-scale reactors and thus deliver results that are more comparable to large-scale fermentations, but with the additional advantages of small size, availability of online cultivation data and the potential for automation. Current microbioreactor technology is analyzed in this review paper, focusing on its industrial applicability, and directions for future research are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Weuster-Botz D, Hekmat D, Puskeiler R, Franco-Lara E (2007) Adv Biochem Eng Biotechnol 105(205):247

    Google Scholar 

  2. Shuler ML, Kargi F (2002) Bioprocess engineering: basic concepts. Prentice Hall, Upper Saddle River

  3. Lye GJ, Ayazi-Shamlou P, Baganz F, Dalby PA, Woodley JM (2003) Trends Biotechnol 21(1):29–37

    Article  CAS  Google Scholar 

  4. Kumar S, Wittmann C, Heinzle E (2004) Biotechnol Lett 26:1–10

    Article  CAS  Google Scholar 

  5. Betts JI, Baganz F (2006) Microb Cell Fact 5:21

    Google Scholar 

  6. Micheletti M, Lye GJ (2006) Curr Opin Biotechnol 17:611–618

    Article  CAS  Google Scholar 

  7. Szita N, Boccazzi P, Zhang Z, Boyle P, Sinskey AJ, Jensen KF (2005) Lab Chip 5:819–826

    Google Scholar 

  8. Zhang Z, Boccazzi P, Choi HG, Perozziello G, Sinskey AJ, Jensen KF (2006) Lab Chip 6:906–913

    Google Scholar 

  9. Lee HLT, Boccazzi P, Ram RJ, Sinskey AJ (2006) Lab Chip 6:1229–1235

    Google Scholar 

  10. Zanzotto A, Szita N, Boccazzi P, Lessard P, Sinskey AJ, Jensen KF (2004) Biotechnol Bioeng 87(2):243–254

    Article  CAS  Google Scholar 

  11. De Jong J (2008) Application of membrane technology in microfluidic devices (Ph.D. thesis). University of Twente, Twente

  12. Zhao YG, Lu WK, Kim SS, Ho ST, Marks TJ (2000) Appl Phys Lett 77(19):2961–2963

    Article  CAS  Google Scholar 

  13. Fleger M, Neyer A (2006) Microelectron Eng 83:1291–1293

    Article  CAS  Google Scholar 

  14. Becker H, Gärtner C (2008) Anal Bioanal Chem 390:89–111

    Article  CAS  Google Scholar 

  15. Tsao CW, Devoe DL (2009) Microfluid Nanofluid 6:1–16

    Article  CAS  Google Scholar 

  16. Mcdonald JC, Whitesides GM (2002) Acc Chem Res 35(7):491–499

    Article  CAS  Google Scholar 

  17. Huang C-W, Lee G-B (2007) J Micromech Microeng 17:1266–1274

    Google Scholar 

  18. Anvari M, Khayati G (2009) J Ind Microbiol Biotech 36:313–317

    Article  CAS  Google Scholar 

  19. Zautsen RRM, Maugeri-Filho F, Vaz-Rossell CE, Straathof AJJ, van der Wielen LAM, de Bont JAM (2009) Biotechnol Bioeng 102:1354–1360

    Article  CAS  Google Scholar 

  20. Purcell EM (1977) Am J Phys 45(1):3–11

    Article  Google Scholar 

  21. Hessel V, Löwe H, Schönfeld F (2005) Chem Eng Sci 60:2479–2501

    Article  CAS  Google Scholar 

  22. Hardt S, Schönfeld F (2007) Microfluidic technologies for miniaturized analysis systems. Springer, New York

  23. Maharbiz MM, Holtz WJ, Howe RT, Keasling JD (2004) Biotechnol Bioeng 85(4):376–381

    Article  CAS  Google Scholar 

  24. Strook AD, Dertinger SKW, Ajdari A, Mezić I, Stone HA, Whitesides GM (2002) Science 295:647–651

    Article  Google Scholar 

  25. Li X, van der Steen G, van Dedem GWK, van der Wielen LAM, van Leeuwen M, van Gulik WM, Heijnen JJ, Krommenhoek EE, Gardeniers JGE, van den Berg A, Ottens M (2008) Chem Eng Sci 63:3036–3046

    Article  CAS  Google Scholar 

  26. Berthier E, Warrick J, Hongmeiy Y, Beebe DJ (2008) Lab Chip 8:852–859

    Google Scholar 

  27. Boccazzi P, Zhang Z, Kurosawa K, Szita N, Bhattacharya S, Jensen KF, Sinskey AJ (2006) Biotechnol Prog 22:710–717

    Article  CAS  Google Scholar 

  28. Olsson A, Stemme G, Stemme E (1996) Sens Actuators A 137:143

    Google Scholar 

  29. Jeong OC, Park SW, Yang SS, Pak JJ (2005) Sens Actuators A 123:453

    Google Scholar 

  30. Fredrickson CK, Fan ZH (2004) Lab Chip 4:526–533

    Google Scholar 

  31. Perozziello G (2006) Doctoral thesis. Technical University of Denmark, Lyngby

  32. Kortmann H, Blank LM, Schmid A (2009) Lab Chip 9:1455–1460

    Google Scholar 

  33. Vojinović V, Cabral JMS, Fonseca LP (2005) Sens Actuators B 114:1083–1091

    Google Scholar 

  34. Petronis S, Stangegaard M, Christensen CBV, Dufva M (2006) Biotechniques 40:368–376

    Article  CAS  Google Scholar 

  35. Maiti TK (2006) IEEE Sens J 6(6):1454–1458

    Article  Google Scholar 

  36. Krommenhoek EE, van Leeuwen M, Gardeniers H, van Gulik WM, van den Berg A, Li X, Ottens M, van der Wielen LAM, Heijnen JJ (2008) Biotechnol Bioeng 99(4):884–892

    Article  CAS  Google Scholar 

  37. Vervliet-Scheebaum M, Ritzenthaler R, Normann J, Wagner E (2008) Ecotoxicol Environ Saf 69:254–262

    Article  CAS  Google Scholar 

  38. Gimbun J, Radiah ABD, Chuah TG (2004) Food Eng 64:277–283

    Article  Google Scholar 

  39. Assael MJ, Antoniadis KD, Wu J (2008) Int J Thermophys 29:1257–1266

    Article  CAS  Google Scholar 

  40. Shin YS, Cho K, Lim SH, Chung S, Park SJ, Chung C, Han DC, Chang JK (2003) J Micromech Microeng 13:768–774

    Google Scholar 

  41. Liu L, Peng S, Niu X, Wen W (2006) Appl Phys Lett 89:223521

    Article  CAS  Google Scholar 

  42. Yamamoto T, Nojima T, Fujii T (2002) Lab Chip 2:197–202

    Google Scholar 

  43. van Leeuwen M, Heijnen JJ, Gardeniers H, Oudshoorn A, Noorman H, Visser J, van der Wielen LAM, van Gulik WM (2009) Chem Eng Sci 64:455–458

    Article  CAS  Google Scholar 

  44. Isett K, George H, Herber W, Amanullah A (2007) Biotechnol Bioeng 98:1017–1028

    Article  CAS  Google Scholar 

  45. PreSens (2009) Noninvasive pH probes. http://www.presens.de/products/brochures/category/sensor-probes/brochure/non-invasive-ph-sensors.html. Accessed 9 March 2009

  46. Microsens (2009) Ion-sensitive field-effect transistor. http://www.microsens.ch/products/chemical.htm. Accessed 9 March 2009

  47. John GT, Goelling D, Klimant I, Schneider H, Heinzle E (2003) J Dairy Res 70:327–333

    Article  CAS  Google Scholar 

  48. Zhang Z, Perozziello G, Boccazzi P, Sinskey AJ, Geschke O, Jensen KF (2007) J Assoc Lab Automat 12(3):143–151

    Google Scholar 

  49. Krommenhoek EE, Gardeniers JGE, Bomer JG, Li X, Ottens M, van Dedem GWK, van Leeuwen M, van Gulik WM, van der Wielen LAM, Heijnen JJ, van den Berg A (2007) Anal Chem 79(15):5567–5573

    Article  CAS  Google Scholar 

  50. Buchenauer A, Hofmann MC, Funke M, Büchs J, Mokwa W, Schnakenberg U (2009) Biosens Bioelecton 24:1411–1416

    Article  CAS  Google Scholar 

  51. Wu MH, Huang SB, Cui Z, Cui Z, Lee GB (2008) Biomed Microdevices 10(2):309–319

    Article  Google Scholar 

  52. Applikon Biotechnology (2009) Micro 24 bioreactor. http://www.applikon-bio.com/index.php?option=com_content&view=article&id=80&catid=43&Itemid=17. Accessed 9 March 2009

  53. Jensen KH, Alam MN, Scherer B, Lambrecht A, Mortensen NA (2008) Opt Commun 281:5335–5339

    Article  CAS  Google Scholar 

  54. Cervera AE, Petersen N, Eliasson Lantz A, Larsen A, Gernaey KV (2009) Biotechnol Progr (in press). doi:10.1021/bp.280

  55. Sartorius BBI Systems (2009) Sartorius FUNDALUX II turbidity sensor. http://www.sartorius-stedim.com/index.php?id=1999. Accessed 9 March 2009

  56. Villain L, Meyer L, Kroll S, Beutel S, Scheper T (2008) Biotechnol Prog 24:367–371

    Article  CAS  Google Scholar 

  57. Papkovsky DB (1995) Sens Actuators B 29:213–218

    Google Scholar 

  58. Islam RS, Tisi D, Levy MS, Lye GJ (2007) Biotechnol Bioeng 99(5):1128–1139

    Article  CAS  Google Scholar 

  59. Ge X, Kostov Y, Rao G (2004) Biotechnol Bioeng 89(3):329–334

    Article  CAS  Google Scholar 

  60. Liebsch G, Klimant I, Frank B, Holst G, Wolfbeis OS (2000) Appl Spectrosc 54(4):548–559

    Article  CAS  Google Scholar 

  61. Scarff M, Arnold SA, Harvey LM, McNeil B (2006) Crit Rev Biotechnol 26:17–39

    Article  CAS  Google Scholar 

  62. Lee HLT, Boccazzi P, Gorret N, Ram RJ, Sinskey AJ (2004) Vib Spectrosc 35:131–137

    Article  CAS  Google Scholar 

  63. Cao E, Firth S, McMillan PF, Gavriilidis A (2007) Catal Today 126:119–126

    Article  CAS  Google Scholar 

  64. Ferstl W, Klahn T, Schweikert W, Billeb G, Schwarzer M, Loebbecke S (2007) Chem Eng Technol 30(3):370–378

    Article  CAS  Google Scholar 

  65. Biomass R&D, Technical Advisory Committee (2006) Vision for bioenergy and biobased products in the United States. http://www.brdisolutions.com/default.aspx Accessed 9 March 2009

  66. European Technology Platform for Sustainable Chemistry, Industrial Biotechnology Section (2005) Homepage. http://www.suschem.org. Accessed 9 March 2009

  67. Riesenberg D, Guthke R (1999) Appl Microbiol Biotechnol 51:422–430

    Article  CAS  Google Scholar 

  68. Åkesson M, Hagander P, Axelsson JP (1999) Biotechnol Tech 13:523–528

    Article  Google Scholar 

  69. de Maré L, Cimander C, Elfwing A, Hagander P (2007) Bioprocess Biosyst Eng 30:13–25

    Article  CAS  Google Scholar 

  70. Sartorius BBI Systems (2009) Biostat Cultibag. http://www.sartorius-stedim.com/index.php?id=4387. Accessed 7 March 2009

  71. Sathuluri RR, Yamamura S, Tamiya E (2008) Adv Biochem Eng Biotechnol 109:285–350

    Google Scholar 

  72. Lennox B, Montague GA, Hiden HG, Kornfeld G, Goulding PR (2001) Biotechnol Bioeng 74:125–135

    Article  CAS  Google Scholar 

  73. Sundström H, Enfors S-O (2008) Bioprocess Biosyst Eng 31:145–152

    Article  CAS  Google Scholar 

  74. Zhang Z, Szita N, Boccazzi P, Sinskey AJ, Jensen KF (2005) Biotechnol Bioeng 92(2):286–296

    Article  CAS  Google Scholar 

Download references

Acknowledgement

The Ph.D. project of Daniel Schäpper is financed by the Novozymes Bioprocess Academy.

Author information

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Technical University of Denmark, 2800, Lyngby, Denmark

    Daniel Schäpper, Muhd Nazrul Hisham Zainal Alam & Krist V. Gernaey

  2. Department of Bioprocess Engineering, Faculty of Chemical and Natural Resources Engineering, Universiti Teknologi Malaysia, Johore, Malaysia

    Muhd Nazrul Hisham Zainal Alam

  3. Department of Biochemical Engineering, University College London, London, WC1E 6BT, UK

    Nicolas Szita

  4. Department of Systems Biology, Technical University of Denmark, 2800, Lyngby, Denmark

    Anna Eliasson Lantz

Authors
  1. Daniel Schäpper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhd Nazrul Hisham Zainal Alam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicolas Szita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Eliasson Lantz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Krist V. Gernaey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Krist V. Gernaey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schäpper, D., Alam, M.N.H.Z., Szita, N. et al. Application of microbioreactors in fermentation process development: a review. Anal Bioanal Chem 395, 679–695 (2009). https://doi.org/10.1007/s00216-009-2955-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-009-2955-x

Keywords

Search

Navigation